This invention relates to the measurement of cadmium in biological specimens and more particularly to the detection and measurement of ultratrace cadmium levels in blood and other biological fluids.
Measurement of cadmium in blood, urine, tissue and other biological specimens at low levels is important for a number of reasons. Cadmium has a long biological half-life and the toxic effects of exposure are cumulative. Chronic exposure to cadmium can irreversibly damage the kidneys. Cadmium is now considered to be a potential carcinogen. Also, recent biomedical research suggests that low-level cadmium exposure from smoking may contribute to osteoporosis.
Cadmium in addition to lead may be found in the working environment, in ambient air, in drinking water, in tobacco smoke and in food. Certain foods may be the major contributors to human exposure to cadmium. Smoking may be an additional significant source of cadmium exposure. Because cadmium accumulates in humans from different sources, biological monitoring has become recognized as a desired way to estimate the total exposure and risks associated with cadmium.
The measurement of the level of toxic metals in human body fluids is often the best way of evaluating undue exposure, whether the source be industrial, environmental or iatrogenic. To be of any use in diagnosing and monitoring exposed individuals, analytical results generated must be reliable (i.e., accurate), and reproducible with time.
The determination of cadmium in biological samples is of considerable interest to health and research organizations. Studies have been conducted to measure and monitor cadmium (and other toxic substances) in body fluids. One study, as reported in "An Interlaboratory Comparison Programme For Several Toxic Substances in Blood and Urine" by Jean-Philippe Weber, in The Science of the Total Environment, (1988) 71, 111-123, was directed to the measurement of cadmium (and other toxic substances) in blood and urine as performed by a number of laboratories. Consistency in the measurements of cadmium even at levels above 5 .mu.g/L was difficult as indicated by the reported coefficients of variation in the order of 30-40%, with higher values for lower concentrations.
The most widely used analytical technique for measuring cadmium in blood and urine samples involves the steps of deproteination and direct analysis by electrothermal atomic absorption spectrophotometry (ETAAS). In general, this technique has provided acceptable consistency of results with samples having a cadmium concentration above about 5 .mu.g Cd/L.
One reason for the difficulty in measuring cadmium at levels of .ltoreq.5 .mu.g/L is that the deproteination or wet-ashing step in the above described technique removes cadmium from its organic environment but does not separate it from inorganic constituents. Sodium and potassium concentrations in normal blood are generally 10.sup.6 times greater than cadmium. When using electrothermal atomic absorption spectrophotometry (ETAAS) with deuterium background correction for the analysis of cadmium in blood, this inorganic environment contributes significantly to the inaccuracy and imprecision of the measurement. Another difficulty associated with measuring cadmium in blood arises from the presence of cadmium as an ubiquitous environmental contaminant. Control or avoidance of cadmium contamination by glassware, plastic ware, reagents and air is of utmost importance for proper accuracy.
In order to evaluate cadmium exposures in an environmental setting, it is important to measure cadmium at low levels (i.e., below about 0.5 .mu.g/L) in blood, urine and other biological specimens. Seawater is also an important medium for measuring cadmium content since cadmium may have an adverse effect on developing fish embryos. Data on cadmium levels, particularly in body fluids, and changes in those levels related to exposure to special environmental conditions, could be of considerable importance in providing early indications of medical problems. Since the toxic effects of exposure are reported to be cumulative, information of this type could also be particularly important in association with tests on young persons to determine early adverse exposure.
Accordingly, one object of this invention is a method of testing biological specimens for low cadmium concentrations. Another object of the invention is a method of testing biological fluids containing high values of alkali metal contaminants for cadmium. Yet another object of the invention is a method for testing biological fluids for low cadmium concentration with improved accuracy. These and other advantages of the invention will become apparent from the following description.